Complement c3 convertase classical pathway. Medical search

Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.

A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.

The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.

A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.

Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.

A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.

Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.

Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).

C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.

Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.

The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.

Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.

The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.

A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.

The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.

A CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.

A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.

A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).

A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.

A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.

A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).

A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.

Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.

A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.

A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.

A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).

A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.

A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.

Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.

A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.

The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.

A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.

The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.

A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.

The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.

Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.

An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).

A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).

Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.

A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.

Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.

The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.

A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.

An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.

Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-

A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.

Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.

GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.

A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.

An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.

Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.

The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.

Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.

A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.

The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.

An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.

Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.

Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.

Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.

Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)

A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.

Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.

A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.

The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.

A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.

Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.

Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.

Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.

Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

Polysaccharides consisting of mannose units.

Proteins prepared by recombinant DNA technology.

Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.

A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.

A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.

Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.

The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.

Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.

Antibodies produced by a single clone of cells.

The rate dynamics in chemical or physical systems.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).

Established cell cultures that have the potential to propagate indefinitely.

A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.

Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.

Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.

Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.

A 19-kDa cationic peptide found in EOSINOPHIL granules. Eosinophil-derived neurotoxin is a RIBONUCLEASE and may play a role as an endogenous antiviral agent.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

Transport proteins that carry specific substances in the blood or across cell membranes.

Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.

Immunoglobulins produced in a response to BACTERIAL ANTIGENS.

Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.

Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.

Physiologically inactive substances that can be converted to active enzymes.

A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.

Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.

A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.

The sum of the weight of all the atoms in a molecule.

The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.

A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.

A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).

Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)

Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.

Proteins isolated from the outer membrane of Gram-negative bacteria.

A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).

The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.

A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.

An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.

ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.

Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.

A plasma protein that circulates in increased amounts during inflammation and after tissue damage.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.

Proteins found in any species of bacterium.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.

The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.

Substances elaborated by bacteria that have antigenic activity.

Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.

A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.

A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.

A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.

A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.

Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Elements of limited time intervals, contributing to particular results or situations.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.

The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)

The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Glycoproteins found on the membrane or surface of cells.

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

A 37-amino acid peptide derived from the C-terminal of GLICENTIN. It is mainly produced by the INTESTINAL L CELLS. Oxyntomodulin can reduce digestive secretions, delay gastric emptying, and reduced food intake.

Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.

Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.

Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.

Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

The process of cleaving a chemical compound by the addition of a molecule of water.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Separation of decay-accelerating and cofactor functional activities of Kaposi's sarcoma-associated herpesvirus complement control protein using monoclonal antibodies. (1/3)

Complement is an essential part of the innate immune system, which clears pathogens without requirement for previous exposure, although it also greatly enhances the efficacy and response of the cellular and humoral immune systems. Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently identified human herpesvirus and the likely aetiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. We previously reported that the KSHV complement control protein (KCP) was expressed on infected cells and virions, and could inhibit complement through decay-accelerating activity (DAA) of the classical C3 convertase and cofactor activity (CFA) for factor I (FI)-mediated degradation of C4b and C3b, as well as acting as an attachment factor for binding to heparan sulphate on permissive cells. Here, we determined the ability of a panel of monoclonal anti-KCP antibodies to block KCP functions relative to their recognized epitopes, as determined through binding to recombinant KCP containing large (entire domain) or small (2-3 amino acid residue) alterations. One antibody recognizing complement control protein (CCP) domain 1 blocked heparin binding, DAA and C4b CFA, but was poor at blocking C3b CFA, while a second antibody recognizing CCP4 blocked C3b CFA and 80% DAA, but not C4b CFA or heparan sulphate binding. Two antibodies recognizing CCP2 and CCP3 were capable of blocking C3b and C4b CFA and heparan sulphate binding, but only one could inhibit DAA. These results show that, while KCP is a multifunctional protein, these activities do not completely overlap and can be isolated through incubation with monoclonal antibodies. (+info)

Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. (2/3)

(+info)

Sushi domain-containing protein 4 (SUSD4) inhibits complement by disrupting the formation of the classical C3 convertase. (3/3)

(+info)

... the classical, lectin, and alternative pathways. Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... "Formation of classical C3 convertase during the alternative pathway of human complement activation". Biokhimiia (Moscow, Russia ...

https://en.wikipedia.org/wiki/C3-convertase

The MASPs cleave C4 and C2, resulting in C3 convertase formation. The alternative pathway of complement activation is typically ... The classical pathway of complement activation is initiated when the C1 complex, made up of C1r and C1s serine proteases, ... Levels of complement are regulated by moderating convertase formation and enzymatic activity. C3 convertase formation is ... C3 convertase activity is also regulated without C3b inactivation, through complement control proteins, including decay- ...

https://en.wikipedia.org/wiki/C3a_(complement)

In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ... C3 convertase. C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement ...

https://en.wikipedia.org/wiki/Complement_component_3

The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... C4b and C2b then bind together to form the classical C3-convertase, as in the classical pathway. Ficolins are homologous to MBL ... C4b and C2b bind to form the classical pathway C3-convertase (C4b2b complex), which promotes cleavage of C3 into C3a and C3b. ...

https://en.wikipedia.org/wiki/Complement_system

... targets the C1s enzyme and inhibits its enzymatic propagation of the classical complement pathway, thereby, ... preventing the formation of the C3-convertase enzyme. The effectiveness of sutimlimab was assessed in a study of 24 adults with ... a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway". Clinical Pharmacology and Therapeutics. ... Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro. This drug is being developed by ...

https://en.wikipedia.org/wiki/Sutimlimab

... alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 ... Consequently, levels of all complement proteins become low. The complement pathway is composed of several subset pathways: the ... classical complement pathway). In brief, the crucial role of C1q in the pathway is its importance as the first protein to start ... in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement ...

https://en.wikipedia.org/wiki/Urticarial_vasculitis

C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. C1q - another part of ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... "Entrez Gene: C1S Complement component 1, s subcomponent". Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, ... Complement+C1s at the US National Library of Medicine Medical Subject Headings (MeSH) Human C1S genome location and C1S gene ...

https://en.wikipedia.org/wiki/Complement_component_1s

In the classical and lectin pathways of complement activation, formation of the C3-convertase and C5-convertases requires ... fragment of C3 convertase in this pathway, C4b2b (NB: some sources now refer to the larger fragment of C2 as C2b, making the C3 ... The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine ... a fragment of complement component C2 produced during C3 convertase formation". Acta Crystallographica D. 65 (Pt 3): 266-274. ...

https://en.wikipedia.org/wiki/Complement_component_2

... classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC ... classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC ... 3.4.21.45: complement factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ... 3.4.21.45: complement factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ...

https://en.wikipedia.org/wiki/List_of_EC_numbers_(EC_3)

... which cleaves the C3 protein. The C3b component of the cleaved C3 binds to C3 convertase (C4b2b) to generate C5 convertase ( ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ...

https://en.wikipedia.org/wiki/Classical_complement_pathway

C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1-inhibitor ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ...

https://en.wikipedia.org/wiki/Outline_of_immunology

... classical or lectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and ... Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane ... thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. ...

https://en.wikipedia.org/wiki/Decay-accelerating_factor

Therefore, unlike the classical complement pathway the TEP1 pathway is antibody independent and instead relies on the presence ... The discovery of C3 like molecules in a diverse range of species suggests that the complement pathway in particular the ... Furthermore, both the TEP1 pathway and the alternative pathway utilise convertase mediated amplification loops to increase ... from a complement-like protein to a complement-like pathway". Cell Host Microbe. 3 (6): 364-74. doi:10.1016/j.chom.2008.05.007 ...

https://en.wikipedia.org/wiki/Thioester-containing_protein_1

C3 and C5 convertase activity is generated upon addition of Factors B and D. The classical pathway C5 convertase is composed of ... Two of the convertases are physiological complement enzymes, associate to the cell-surface and mediate the classical pathway ( ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2a). The formation of the alternative pathway ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ...

https://en.wikipedia.org/wiki/C5-convertase

Antibodies can also trigger the classical pathway - one of the three pathways of the complement cascade. Briefly, the C1 ... On the other hand, C3 protein can opsonize pathogens and bind to C3 convertase to catalyze the formation of C5 convertase to ... The formation of complement proteins (C3a, C3b, C5a, C5b, etc.) ultimately congregates into a membrane-attack complex to lyse ... protein attaches to the pathogen surface and the antibody-antigen complex that culminates in the generation of C3 convertase, ...

https://en.wikipedia.org/wiki/Passive_antibody_therapy

The classical pathway C3-convertase (C4bC2b complex) is created, which promotes cleavage of C3. Janeway, CA Jr; Travers P; ... is a protein complex involved in the complement system. It is the first component of the classical complement pathway and is ... Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ...

https://en.wikipedia.org/wiki/C1_complex

In all three pathways of complement activation, there is a target for the protease to manipulate. In the classical pathway, ... the protein is cleaved two amino acid residues away from the native site that is recognized by the host C3 convertase. The ... C3 is another major target of aureolysin. The active site has a high affinity for C3 and will cleave it into C3a and C3b ... April 2011). "Staphylococcus aureus Metalloprotease Aureolysin Cleaves Complement C3 To Mediate Immune Evasion". Journal of ...

https://en.wikipedia.org/wiki/Aureolysin

This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... and C3 glomerulonephritis (Dense Deposit Disease or MPGN Type II). Classical complement pathway Lectin pathway Conrad DH, Carlo ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... After the creation of C5 convertase (either as (C3b)2BbP or C4b2a3b from the classical pathway), the complement system follows ...

https://en.wikipedia.org/wiki/Alternative_complement_pathway

... but C3 plays a central role in all three of these pathways (see the pages for the classical pathway, alternative pathway, and ... the lectin pathway). Each of these pathways involves the formation of a C3-convertase, which will cleave C3 molecules into C3a ... Both primary and secondary C3 deficiency are characterized by low levels or absence of C3. Complement component 3 (C3) is a ... C3 is one of over 30 complement proteins circulating in the blood. C3 circulates in an inactive form but can be activated in ...

https://en.wikipedia.org/wiki/Complement_3_deficiency

The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... and initiate the formation of a C3-convertase. The subsequent complement cascade catalyzed by C3-convertase results in creating ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...

https://en.wikipedia.org/wiki/Mannan-binding_lectin

C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds ... It inhibits the action the classical and the lectin pathways, more specifically C4. It also has ability to bind C3b. ... Complement+C4b-Binding+Protein at the US National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with ... The genes coding for C4BP α-chain (C4BPA) and β-chain (C4BPB) are located in the regulators of complement activation (RCA) gene ...

https://en.wikipedia.org/wiki/C4b-binding_protein

... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ... In the classical pathway, the complement component-hereafter abbreviated by the "C" preceding the protein number- termed C1s, a ...

https://en.wikipedia.org/wiki/Complement_component_4

... classical pathway, alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation ... In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. The C1 complement ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ... Incorporation of an additional C3b into the C3bBb C3 convertase leads to the formation of C3Bb3b C5 convertase. Once cleaved ...

https://en.wikipedia.org/wiki/C3b

... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 - complement c3-c5 convertases, alternative pathway MeSH ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... pathway MeSH D12.776.124.486.274.860.387.750.750 - complement c5 convertase, classical pathway MeSH D12.776.124.486.274.860. ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D12.776.124)

... the C3 convertase generating protease of the MBLectin complement activating pathway". Immunobiology. 199 (2): 348-57. doi: ... MASP-2 is involved in the complement system. MASP-2 is very similar to the C1s molecule, of the classical complement pathway, ... Petersen SV, Thiel S, Jensenius JC (2001). "The mannan-binding lectin pathway of complement activation: biology and disease ... MASP1 (protein) Mannan-binding lectin Mannan-binding lectin pathway (lectin pathway) GRCh38: Ensembl release 89: ...

https://en.wikipedia.org/wiki/MASP2_(protein)

Three biochemical pathways activate the complement system: the classical complement pathway, the alternate complement pathway, ... These processes differ only in the process of activating C3 convertase, which is the initial step of complement activation, and ... and the mannose-binding lectin pathway. The classical complement pathway typically requires antibodies for activation and is a ... 12 of which are directly involved in the complement pathways. The complement system is involved in the activities of both ...

https://en.wikipedia.org/wiki/Humoral_immunity

The classical pathway, lectin pathway, and alternative pathway of complement are all involved in glomerulonephritis, depending ... C1q, the first component of the complement system, encounters conformational change that leads to C3 convertase breaking C3 ... There are no current clinical trials for DPGN happening.[citation needed] Activating complement pathways plays a large role in ... There are currently drugs available that will target the complement pathway. It has been proposed that if fluorescently tagged ...

https://en.wikipedia.org/wiki/Diffuse_proliferative_nephritis

If it is not then inactivated, it will combine with C2a to form the classical C3 convertase (C4bC2a) on the surface of the ... Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ...

https://en.wikipedia.org/wiki/Lectin_pathway

MASP2 and initiate the lectin pathway of complement activation which is somewhat similar to the classical complement pathway. ... C4b and C2a are known as the C3 convertase. C3 is cleaved into its a and b subunits, and C3b binds the convertase. These ... dependent signaling pathway. MyD88 - dependent pathway is induced by various PAMPs stimulating the TLRs on macrophages and ... dependent pathway and triggers the signaling through NF-κB and the MAP kinase pathway and therefore the secretion of pro- ...

https://en.wikipedia.org/wiki/Pattern_recognition_receptor

In classical type I lissencephaly, neuronal migration begins but is unable to continue to completion. This process is likely ... Many of the specifics of this pathway are still being investigated. It is not yet known if Dab1 is phosphorylated as a result ... Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (May 2009). "Polymorphisms in C2, CFB and C3 are associated with progression ... "The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family ...

https://en.wikipedia.org/wiki/VLDL_receptor

Name: complement component 2 (within H-2S). Synonyms: classical-complement pathway C3/C5 convertase ...

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=38808

They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE. ... Complement C3-C5 Convertases. *Complement C3-C5 Convertases, Alternative Pathway. *Complement C3-C5 Convertases, Classical ... Complement C3-C5 Convertases [D12.776.124.486.274.045.387]. *Mannose-Binding Protein-Associated Serine Proteases [D12.776. ... The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. ...

https://connects.catalyst.harvard.edu/Profiles/display/Concept/Mannose-Binding%20Protein-Associated%20Serine%20Proteases

Complement C3 Convertase, Classical Pathway Entry term(s). C3 Convertase (C4b2a) C3 Convertase, Classical Classical C3 ... Classical pathway complement C3 convertase Entry term(s):. C3 Convertase (C4b2a). C3 Convertase, Classical. Classical C3 ... Complement C3-C5 Convertases, Classical Pathway [D12.776.124.486.274.045.387.750] Complement C3-C5 Convertases, Classical ... Complement C3 Convertase, Classical Pathway Descriptor Spanish: C3 Convertasa de la Vía Clásica del Complemento Spanish from ...

https://decs.bvsalud.org/en/ths/resource/?id=50833

... promoting the activation of the classical complement pathway and interacts with phagocytic cells. The primary stimulus for CRP ... C1r and C1s serine proteases are then activated and fragment C2 and C4 to form C3 convertase. This enzymatic complex becomes ... administered a C3 complement inhibitor (CR2-Crry) in MRL/lpr mice from 16 to 24 weeks of age.[58] CR2 binds to C3 deposited ... compared the selective inhibition of the alternative pathway in comparison with the inhibition of all C3 activation pathways.[ ...

https://www.medscape.com/viewarticle/817430_4

... which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of ... The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, ... The complement system, antibodies, and antimicrobial proteins and peptides (APPs), can directly interact with potential ... C3 convertase cleavage of C3 generates C3b, the primary effector molecule of the complement system, and cleavage product C3a, a ...

https://www.frontiersin.org/articles/10.3389/fimmu.2014.00457/full

Complement 1-4 and C3/C5 convertase of the classical pathway together with clusterin and vitronectin were associated with a ... 3c). Interestingly, complement 8 alpha chain, complement 9 and C3/C5 convertase from the alternative pathway showed the same ... Likewise, several components of the complement system (C1, C2, C3, C4 and C7) showed the same abundance behavior as described ... 4c), which indicates activation of the complement system via the alternative pathway and consequently the formation of the ...

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03441-4

The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, ... Crry demonstrates decay-accelerating activity in both the classical and alternative pathways of complement as well as cofactor ... The rodent complement protein, CR1-related y (Crry), is a potent inhibitor of the pivotal C3 convertase of the complement ... The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, ...

https://journals.aai.org/jimmunol/article/175/12/8312/73109/Complement-Dependent-Apoptosis-and-Inflammatory

Watch a video to learn how C1 is activated initiating the classical complement pathway creating chronic hemolysis and ... The classical and lectin pathways cleave C2 and C4 to form C3 convertase. The alternative pathway relies on separate factors to ... It also leads to activation of the classical complement pathway. Now we are going to talk about complement and complement ... form C3 convertase. Once active, C3 convertase initiates the complement response. Cleaved active products of C3 and C5 drive ...

https://www.understandingcad.com/mechanism-cold-agglutinin-disease

The C2 gene provides instructions for making the complement component 2 protein. Learn about this gene and related health ... Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. Biochemistry. ... Without this protein to form C3 convertase, activation of the complement system is stalled. As a result, the complement ... The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. Acta Crystallogr D Biol ...

https://medlineplus.gov/genetics/gene/c2/

... complement can be activated through three somewhat distinct pathways, each one converging at a C3 Convertase. Complement will ... Antibody Triggers the Classical Pathway; Carbohydrates Trigger the Lectin Pathway; The Alternative Pathway is triggered ... a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the ... which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction ...

https://downhouse.software/category/immunology/complement/

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions ... which is the C3 convertase of the classical pathway. (In some texts the C2a is referred to as the larger subunit remaining with ... ACTIVATION OF THE CLASSICAL COMPLEMENT PATHWAY. A complement cascade similar to that of the alternative pathway can be ... The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization ...

https://www.pharmacy180.com/article/activation-of-the-classical-complement-pathway-498/

Learn about the three pathways lead to complement activation and some of their key inhibitors. ... C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). C2a in the convertase complex cleaves C3 ... The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. This complex cleaves C5 ... The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. This complex cleaves C5 ...

https://www.abcam.com/pathways/complement-cascade-and-its-inhibitors

... classical, lectin, and alternative) exist. These pathways converge in the generation of the C3 convertase, which is responsible ... which is the alternative pathway C3 convertase. Human complement factor D is synthesized as a 253 amino acid precursor that ... Complement factor D deficiency is associated with low activity of the alternative complement pathway and low capacity to ... Complement factor D, also known as adipsin, is a serine protease that is indispensable for the initiation of complement ...

https://nexelis.com/our-services/biomarkers/menu/adipsin-complement-factor-d/

has been linked to the classical pathway, type II MPGN is associated with overactive AP complement activity,76 often due to the ... presence of an immunoglobulin termed C3 nephritic factor that binds to the AP C3 convertase and delays its inactivation.72 ... 72 MPGN type I has subendothelial immune complexes with C1q and is associated with classical pathway complement activation.72, ... ANCA-induced neutrophil activation and initiation of the AP complement system remains to be elucidated, and whether anti- ...

https://atpase-receptor.com/index.php/2019/01/

... classical, alternative, and lectin [111]. Proteolytic cleavage of C3 by C3 convertase represents the final common pathway of ... it is conceivable that targeting more proximate complement pathway targets in the upstream activation cascades (e.g. C3 or C4) ... The binding of C3b to C3 convertase generates C5 convertase, which in turn cleaves C5 to generate the terminal anaphylatoxins, ... Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proc Am Thorac Soc 2007; 4: ...

https://openres.ersjournals.com/content/6/4/00405-2020

Complement can be activated in three different ways, one of which is the classical pathway. The classical pathway for ... Indeed, C3 convertase and C5 convertase are both potential complement therapeutic targets in the treatment of related diseases ... "and the complement cascade cannot be activated without the catalysis of several enzymes, among which C3 convertase and C5 ... which mainly include verification of C5 convertase activity, C5 convertase deficiency identification, and C5 convertase ...

http://www.srinagarmagazine.in/story/647358/creative-biolabs-offers-innovative-solutions-for-complement-therapeutics.html

http://www.madurai-news.in/story/144669/creative-biolabs-offers-innovative-solutions-for-complement-therapeutics.html

http://www.itanagarnews.in/story/150584/creative-biolabs-offers-innovative-solutions-for-complement-therapeutics.html

http://news.sharemarketnewslive.com/story/401722/creative-biolabs-offers-innovative-solutions-for-complement-therapeutics.html

... produces the classical pathway C3 convertase C .. class switching: The process by which a B‐cell changes the class but not ... alternative pathway (of complement activation): Activation pathway involving complement components C3, factor B, factor D, and ... classical pathway (of complement activation): Activation pathway involving complement components C1, C2, and C4 that, following ... generates the alternative pathway C3 convertase C3bBb.. anaphylatoxin: A substance (e.g., C3a, C4a, or C5a) capable of directly ...

https://www.roitt.com/glossary.asp

... the classical (CP), lectin (LP), and alternative (AP) pathways (AP). Each pathway converges on C3 cleavage to produce the ... C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. This C3 ... Complement, IgA nephropathy, Alternative complement pathway, Mannan binding lectin complement pathway, IgAN pathogenesis, IgAN ... It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version ...

https://www.alliedacademies.org/articles/initial-findings-suggest-that-complementtargeted-treatments-could-help-with-iga-20090.html

The lectin pathway of complement is an important component of innate immunity. Its activation has been thought to occur via ... followed by MASP-2 autoactivation and cleavage of C4 and C2 generating the C3 convertase. MASP-1 and MASP-3 are related ... it appears that MASP-1 and MASP-2 act in a manner analogous to that of C1r and C1s of the classical pathway. ... MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary C2 cleavage. In mice, MASP-1 and MASP-3 have been ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:Defici%C3%AAncias+do+Desenvolvimento/imunologia

Alternate Pathway. In alternate pathway, C3 is activated directly with no role of earlier complement components. It does not ... Classical Pathway. Classical pathway is usually initiated by reaction of antibody (IgG or IgM) with antigen (e.g. red cells). ... C3 convertase) is formed. The C4b2a complex attached to cell membrane has enzymatic activity and can cleave several hundred C3 ... There are three pathways of complement activation: classical, alternate and mannose-binding pathway (Fig. 1.24). ...

https://www.jaypeedigital.com/eReader/chapter/9789350901847/ch1

I remember sitting in the lecture about the classical complement pathway and none of us had any idea what was going on. The ... saying different variation of numbers and letters such as C4b2a and how that is the C3 convertase which forms the C5 convertase ... However, if you make a poster flow chart the complement system becomes much easier to understand and learn. ... Unit 3 - Cardiovascular and Respiratory introduces some complex pathways such as intracellular signaling which comes up in a ...

https://teaandtablets.home.blog/2019/09/23/first-year-pharmacy-course-modules/

Activation of the complement system occurs via the alternative, classical (antibody requiring), or lectin pathways and while ... the initial steps vary for each pathways they all lead to the formation of C3. C3 is cleaved by C3 convertase to form C3b which ... Extrinsic Pathway and Tissue Factor Release. The extrinsic pathway is so named because it requires TF which is located in ... Complement Disorders and Thrombosis. Deficiencies of complement components greatly increase the risk of infection by Neisseria ...

https://scholars.direct/Articles/public-health/aphr-4-020.php?jid=public-health

... diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement ... To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber ... modulate human complement system pathways. Lyophilized venom and toxin samples solubilized in phosphate buffered saline were ... did not affect the hemolytic activity of the classical pathway, but slightly decreased the hemolytic activity of the ...

https://jvat.biomedcentral.com/articles/10.1186/s40409-015-0026-7

C3 Convertase, Classical use Complement C3 Convertase, Classical Pathway C3 Convertases, Complement use Complement C3-C5 ... C3 Convertase (C3bBb) use Complement C3 Convertase, Alternative Pathway C3 Convertase (C4b2a) use Complement C3 Convertase, ... C5 Convertase, Classical use Complement C5 Convertase, Classical Pathway C5 Convertases, Complement use Complement C3-C5 ... C3 Convertase Activator use Complement Factor D C3 Convertase, Alternative Pathway use Complement C3 Convertase, Alternative ...

https://decs.bvs.br/I/DeCS2017_Alfab-C.htm

... the alternative complement pathway by blocking formation and accelerating the decay of alternative pathway C3 convertases; it ... The genetic variants explain about half of the classical sibling risk of AMD, and commercial genetic testing for some AMD risk ... complement factor I (CFI), complement factor 9 (C9), and complement factor 3 (C3) genes. [22] ... 11] as well as other genes: factor B (BF)/complement component 2 (C2), [11, 12] complement component 3 (C3), [13, 14] and ...

https://www.staging.medscape.com/answers/1940442-168526/what-is-the-role-of-complement-modulating-agents-in-the-treatment-of-age-related-macular-degeneration-amd

https://emedicine.staging.medscape.com/article/1940442-overview

It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... Complement C1 Inactivator Proteins [D12.776.124.486.274.920.250] * Complement C3 Nephritic Factor [D12.776.124.486.274.920.287] ... A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. ...

https://meshb-prev.nlm.nih.gov/record/ui?ui=D050716

The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. (frontiersin.org)
The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. (frontiersin.org)
Additionally, several classes of proteins, including immunoglobulins (Igs), the complement system, and anti-microbial proteins and peptides (APPs), aid in the innate response to invading microorganisms and display age-dependent maturation (Figure 1 ). (frontiersin.org)
Lower levels of complement proteins and anti-microbial proteins and peptides contribute to neonatal susceptibility to infection, while elevated levels of adenosine, adiponectin, and adrenomedullin in neonatal blood may influence immune cell polarization. (frontiersin.org)
Prominent deposition of complement proteins C3 and C9 in brains of MRL/ lpr mice was indicative of complement activation and was significantly reduced by Crry. (aai.org)
The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
Together, these proteins form a complex called C3 convertase, which triggers further activation of the pathway, allowing the proteins of the complement system to participate in an immune response. (medlineplus.gov)
The host proteins that serve key regulatory functions within the alternative pathway (DAF, CR1 factor I, CD59) also serve similar functions within the classical pathway. (pharmacy180.com)
The complement system comprises approximately 30 circulating plasma proteins, as well as cell-surface receptors, that function as part of the innate and adaptive immune system to eliminate pathogens. (nexelis.com)
In IgA nephropathy, complement proteins in the circulation have also been studied and found to have predictive relevance. (alliedacademies.org)
Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
Complement consists of over 50 proteins that either circulate in blood, the lymph and interstitial fluids, or are expressed on cells in mostly pro-enzyme and non-activated states. (hapres.com)

The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. (harvard.edu)
Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. (abcam.com)

A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY . (bvsalud.org)
Once triggered, a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the insoluble C3b, which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction, and also a C5 convertase. (downhouse.software)
Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment C3b once activated [ 1 ][ 2 ]. (alliedacademies.org)

C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). (abcam.com)

Recruitment of Human C1 Esterase Inhibitor Controls Complement Activation on Blood Stage Plasmodium falciparum Merozoites. (harvard.edu)
Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. (harvard.edu)
The role of complement activation in the brains of MRL/ lpr lupus mice was determined using the potent C3 convertase inhibitor, CR1-related y (Crry), administered both as an overexpressing Crry transgene and as Crry-Ig. (aai.org)
Furthermore, Creative Biolabs offers custom solutions and services based on the C5 convertase to meet specific demands from global clients, which mainly include verification of C5 convertase activity, C5 convertase deficiency identification, and C5 convertase inhibitor development. (srinagarmagazine.in)

Complement factor D deficiency is associated with low activity of the alternative complement pathway and low capacity to opsonize bacteria. (nexelis.com)

Upon activation through reversible substrate-induced conformational change into an active enzyme, factor D functions to cleave the C3b-bound factor B, resulting in the formation of C3bBb complex, which is the alternative pathway C3 convertase. (nexelis.com)
Activation pathway involving complement components C3, factor B, factor D, and properdin that, in the presence of a stabilizing activator surface such as microbial polysaccharide, generates the alternative pathway C3 convertase C3bBb. (roitt.com)
Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. (cusabio.com)

When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein attaches (binds) to a similar protein called complement component 4. (medlineplus.gov)
Once this occurs, a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent Fc domains in the antibody-antigen complex. (pharmacy180.com)
A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)
The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. (abcam.com)
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a). (nih.gov)

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)
C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
It is well known that the complement system functions as a 'complement' of the immune system, playing an important role in immune response, pathogen clearance, and inflammation," according to a scientist at Creative Biolabs, "and the complement cascade cannot be activated without the catalysis of several enzymes, among which C3 convertase and C5 convertase are considered the most important ones. (srinagarmagazine.in)
These findings point to the complement cascade as a viable therapy target for chronic renal disease. (alliedacademies.org)
Several genes not involved in the complement cascade have also been implicated. (medscape.com)
Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
Sensing of pathogens or danger by one or more of the three activation pathways, the classical, the lectin, or the alternative complement pathway, triggers activation of the system in a cascade-like fashion. (hapres.com)

The classical pathway can additionally lead to complement protein deposition on insoluble antibody- antigen immune complexes circulating within blood, and in doing so promote the clearance of such potentially harmful complexes by Kupffer cells of the liver. (pharmacy180.com)
Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)

Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. (harvard.edu)
Crry prevented the increased expression of these inflammatory molecules, indicating that the changes were complement dependent. (aai.org)
Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. (medlineplus.gov)
This culminates in the cleavage of the core complement effector molecules C3 and C5 into the bio-active anaphylatoxins C3a and C5a and the opsonins C3b and C5b. (hapres.com)

This C3 convertase is stabilised by Properdin. (alliedacademies.org)

Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
Work on better defining the instructive role of complement on adaptive immune cells led to the somewhat surprising finding that these complement effects were mostly independent of liver-derived complement but rather mediated by locally produced and activated complement-for example, C3 and C5 secreted by APCs and then activated in the extracellular space [8-10] . (hapres.com)

Genes encoding products involved in complement control and interaction with immune complexes are found within these regions. (alliedacademies.org)
[ 21 ] Such rare variants have been described in the complement factor H ( CFH ), complement factor I ( CFI ), complement factor 9 ( C9 ), and complement factor 3 ( C3) genes. (medscape.com)

In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. (understandingcad.com)
The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
Creative Biolabs can provide custom services based on targets of the classical pathway and a full range of therapeutical antibodies, inhibitors, and soluble complement regulators, such as C1 inhibitors, C3 inhibitors, C5 inhibitors, and C5aR inhibitors. (srinagarmagazine.in)

Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)

This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)

These pathways converge in the generation of the C3 convertase, which is responsible for the initiation of a series of events leading to the generation of bacterial opsonin (that facilitates the phagocytosis of opsonized pathogens), anaphylatoxins (that mediate inflammation), and the formation of the terminal membrane attack complex (that induces the lysis of pathogens or cells). (nexelis.com)
These 3 pathways converge at the component C3. (medscape.com)

MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. (harvard.edu)

In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)

The presence of C3 distinguishes IgA nephropathy from glomerular IgA deposition in the asymptomatic stage. (alliedacademies.org)

Human complement factor D is synthesized as a 253 amino acid precursor that contains a signal peptide (aa 1-20), a five-residue activation/pro-peptide (aa 21-25), and the mature chain (aa 26-253). (nexelis.com)
The present study aimed to assess whether Bothrops jararacussu and Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways. (biomedcentral.com)

This C3 convertase molecule is distinct from that within the alternative pathway, but it is from this point onwards that parallels can be drawn between the two cascades. (pharmacy180.com)

The complement system is a key player in innate immunity as well as a powerful link between innate and adaptive immunity. (alliedacademies.org)
Although complement was initially considered only a key constituent of innate immunity, due to its critical role in delivering co-stimulatory signals via engagement of complement receptors on antigen presenting cells (APCs) or directly on B and T cells, it is now also widely recognized as a required functional bridge between innate and adaptive immunity [5-7] . (hapres.com)

The complement system is a powerful arm of innate immunity that protects tissues against invading pathogens. (aai.org)
Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)
Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
The classical complement system is engrained in the mind of scientists and clinicians as a blood-operative key arm of innate immunity, critically required for the protection against invading pathogens. (hapres.com)

The C1s subunit then enzymically cleaves the bound C2a to generate on the membrane a new complex termed C4b2b, which is the C3 convertase of the classical pathway. (pharmacy180.com)
C2a in the convertase complex cleaves C3 releasing C3a and C3b. (abcam.com)

Complement factor D, also known as adipsin, is a serine protease that is indispensable for the initiation of complement activation via the alternative pathway. (nexelis.com)
The Complement Factor D assay employs the quantitative sandwich enzyme immunoassay technique. (nexelis.com)
Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. (nexelis.com)
It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version known as iC3b (FI). (alliedacademies.org)
This process has been attributed to tissue factor (TF) mediated thrombin generation and formation of fibrin clots (extrinsic pathway) [ 3 , 4 ]. (scholars.direct)
The common coding variant Y402H in the complement factor H ( CFH ) gene was the first identified. (medscape.com)
A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)

The C2 gene provides instructions for making the complement component 2 protein. (medlineplus.gov)
At least five mutations in the C2 gene have been found to cause complement component 2 deficiency. (medlineplus.gov)
More than 90 percent of people with complement component 2 deficiency have a mutation that deletes 28 DNA building blocks (nucleotides) from the C2 gene. (medlineplus.gov)
A) Gene Ontology (Move) category nucleotide-binding domains, leucine rich do it again filled with receptor signaling pathway. (baxkyardgardener.com)
A) Gene Ontology (GO) category nucleotide-binding domain name, leucine rich repeat made up of receptor signaling pathway. (baxkyardgardener.com)

These findings present the exciting possibility that complement inhibition is a therapeutic option for lupus cerebritis. (aai.org)
1. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. (understandingcad.com)
CCN5/WISP2-induced inhibition of miR-10b expression in breast cancer cells is mediated through the inhibition of the JNK-HIF1A-TWIST1 signaling pathway [26]. (globaltechbiz.com)

Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)
The complement system is part of the innate immune system. (medscape.com)

The Alternative Pathway is triggered spontaneously. (downhouse.software)
Key steps in the activation of the classical pathway are shown in Figure 9.7, where this pathway is also compared to the alternative pathway. (pharmacy180.com)
However, in contrast to the alternative pathway the activation step in the classical pathway requires specific antibody-antigen interactions. (pharmacy180.com)
The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization, leucocyte activation and membrane lysis of target cells. (pharmacy180.com)
The presence of two complement pathways provides for rapid (alternative) and specific (classical) activation of a key defence mechanism, and offers greater protection against the development of microbial resistance mechanisms. (pharmacy180.com)
Three pathways of complement activation (classical, lectin, and alternative) exist. (nexelis.com)
In renal biopsy specimens, markers indicating the activation of the alternative and mannan-binding lectin (MBL) pathways are linked to disease activity and portend a worse renal outcome. (alliedacademies.org)
Complement is found in the bloodstream in a physiologically inactive state and can be triggered by three mechanisms: the classical (CP), lectin (LP), and alternative (AP) pathways (AP). (alliedacademies.org)
Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. (biomedcentral.com)
At the highest concentration tested (120 μg/mL), B. jararacussu and B. pirajai crude venoms inhibited the hemolytic activity of the classical pathway (65.3 % and 72.4 %, respectively) more strongly than they suppressed the hemolytic activity of the alternative pathway (14.2 and 13.6 %, respectively). (biomedcentral.com)
BpirLAAO-I (50 μg/mL) inhibited 24.3 and 12.4 % of the hemolytic activity of the classical and alternative pathways, respectively. (biomedcentral.com)
[ 3 ] The existence of multiple, complement-related AMD risk alleles has lent further support to this theory and has shed light on the role of uncontrolled alternative complement pathway activation in this disease. (medscape.com)
The alternative pathway is activated in an antibody-independent manner. (medscape.com)
Further, and based on those new aspects of complement activity, we move into more uncharted areas and discuss a hypothetical alternative to the currently accepted model on how the complement system may have evolved and finally outline some of the key questions and challenges in this exciting new research area. (hapres.com)

This mutation prevents the production of any complement component 2 protein. (medlineplus.gov)
It is unclear how complement component 2 deficiency leads to increased susceptibility to autoimmune disorders. (medlineplus.gov)
It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency. (medlineplus.gov)
Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. (medlineplus.gov)
The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (medlineplus.gov)
The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)

Recent case reports demonstrating the efficacy of the humanised anti-C5 monoclonal antibody eculizumab support this notion, but more research into the involvement of complement in IgA nephropathy is needed to guide future treatment strategies. (alliedacademies.org)
The classical pathway is triggered by interaction of the Fc portion of an antibody (immunoglobulin [Ig] M, IgG1, IgG2, IgG3) or C-reactive protein with C1q. (medscape.com)
Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)

This pathway activates NF-B [85]. (baxkyardgardener.com)

An intricate system regulates complement activity. (medscape.com)

New York, USA - November 21, 2022 - Complement-based drug discovery and development has received significant interest and attention from global scientists dedicated to studying complement therapeutics, which have dramatically expedited the development of complement therapeutics. (srinagarmagazine.in)

Indeed, C3 convertase and C5 convertase are both potential complement therapeutic targets in the treatment of related diseases, such as hemolytic uremic syndrome (HUS), which is induced by the down-regulation of C5 convertase blocking. (srinagarmagazine.in)
The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system. (biomedcentral.com)

As such, they are distinctly innate mediators of immunity and are specifically capable of fixing complement on their bacterial targets. (downhouse.software)
The growing notion that compartmentalization of complement-mediated activity in immunity may exist was then supported by the discovery of an intracellularly generated and functioning complement system in human CD4 + and CD8 + T cells [11,12] . (hapres.com)

Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system by B. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. (biomedcentral.com)

Complement activation releases inflammatory mediators that can induce apoptosis. (aai.org)
The functions of complement include the attraction of inflammatory cells, opsonization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). (abcam.com)
Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked by Bothrops snakes. (biomedcentral.com)

Without this protein to form C3 convertase, activation of the complement system is stalled. (medlineplus.gov)
Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. (medlineplus.gov)
In physiological situations, the AP is always active at low levels and is responsible for complement system functioning. (alliedacademies.org)
To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber model. (biomedcentral.com)
Rare genetic variants in the complement system have also been found to play an important role in AMD. (medscape.com)
The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
These findings underscore the duality of the complement system. (medscape.com)
Knowledge about the complement system is expanding. (medscape.com)
Recent work, however, has defined a novel and unexpected role for an intracellular complement system-the complosome-in the regulation of key metabolic events that underlie peripheral human T cell survival as well as the induction and cessation of their effector functions. (hapres.com)
This review summarizes the current knowledge about the emerging vital role of the complosome in T cell metabolism and discusses how viewing the evolution of the complement system from an "unconventional" vantage point could logically account for the development of its metabolic activities. (hapres.com)
The complement system is generally considered among the evolutionary oldest parts of our immune system. (hapres.com)
Likely the most exciting observation though about intracellular complement-coined the complosome to set it apart from the liver-derived and serum-circulating complement system [13] -is the finding that it unexpectedly serves key roles in single cell metabolism [12, 14,15] . (hapres.com)

Serum serine proteases which participate in COMPLEMENT ACTIVATION. (harvard.edu)

Emerging evidence suggests that KLF4 inhibits the Notch signaling pathway [17,37,38]. (globaltechbiz.com)

The tick-over mechanism is the result of spontaneous and continuous hydrolysis of C3, which causes conformational changes in C3. (alliedacademies.org)

[ 4 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)

Complement activity can activate C5, leading to intravascular hemolysis and chronic inflammation. (understandingcad.com)

Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)

In summary, complement can be activated through three somewhat distinct pathways, each one converging at a C3 Convertase. (downhouse.software)

Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)

In the classical pathway the initiating step is the specific binding of IgG or IgM to antigen. (pharmacy180.com)

Furthermore, microarray analysis revealed complement-dependent up-regulation of glutamate receptor (AMPA-GluR) expression in lupus brains, which was also validated for AMPA-GluR1 mRNA and protein. (aai.org)
Noris M, Remuzzi G. Overview of complement activation and regulation. (understandingcad.com)

The pathway starts with a protein called C1 binding to the red blood cell. (understandingcad.com)

If not controlled, this process can rapidly amplify, leading to the activation of the terminal pathway, which is marked by the release of C5a and the creation of the membrane attack complex (MAC - C5b9). (alliedacademies.org)

The classical pathway for complement activation is a major contributor to the defense against infections, the removal of necrotic cells, and the maintenance of homeostasis. (srinagarmagazine.in)
The extrinsic pathway is so named because it requires TF which is located in vascular smooth muscle cells, pericytes, and adventitial fibroblasts "extrinsic" to the endothelium of blood vessels to initiate coagulation. (scholars.direct)
In this brief feature article, we give a succinct overview of our current understanding about the mechanistic roles of intracellular complement during the immunometabolic adaptions underlying the life cycle of human T cells. (hapres.com)
Metabolism plays an integral role in CD4 + T cell responses with naïve cells, the various effector cell subtypes (for example, T helper type (Th) 1, Th2, Th17 and regulatory T cells), and memory T cells each utilizing their own constellation of metabolic pathways, with differing dependences on influx/efflux of nutrients, their subsequent usage and the generation of downstream metabolic products. (hapres.com)

Anatomy19

Organisms12

Diseases12

Chemicals and Drugs136

Analytical, Diagnostic and Therapeutic Techniques and Equipment22

Phenomena and Processes43

Disciplines and Occupations1

Information Science3

Separation of decay-accelerating and cofactor functional activities of Kaposi's sarcoma-associated herpesvirus complement control protein using monoclonal antibodies. (1/3)

Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. (2/3)

Sushi domain-containing protein 4 (SUSD4) inhibits complement by disrupting the formation of the classical C3 convertase. (3/3)

Complement Pathway, Classical

Complement C3

Complement C4

Complement Activation

Complement C1q

Complement C3-C5 Convertases

Complement C2

Complement C4b

Complement C3b

Complement Pathway, Alternative

Complement C4a

Complement System Proteins

Complement C5

Complement Activating Enzymes

Complement C3a

Complement Inactivator Proteins

Complement C1

Proprotein Convertase 2

Complement C5a

Proprotein Convertase 1

Complement Factor B

Complement C1s

Complement C6

Complement C5 Convertase, Classical Pathway

Complement C3d

Complement C3c

Receptors, Complement

Complement C9

Complement C1r

Complement C3 Convertase, Classical Pathway

Proprotein Convertase 5

Complement Membrane Attack Complex

Proprotein Convertases

Properdin

Complement C2a

Complement Factor D

Complement C7

Complement C2b

Complement C3 Convertase, Alternative Pathway

Complement C5b

Complement C1 Inactivator Proteins

Complement Factor H

Complement C4b-Binding Protein

Receptors, Complement 3b

Complement Hemolytic Activity Assay

Complement C3b Inactivator Proteins

Hemolysis

Complement Factor I

Complement C3 Nephritic Factor

Complement C3-C5 Convertases, Classical Pathway

Subtilisins

Furin

Complement Inactivating Agents

Antigens, CD55

Complement C8

Complement C1 Inhibitor Protein

Opsonin Proteins

Antigen-Antibody Complex

Complement Pathway, Mannose-Binding Lectin

Immunoglobulin G

Receptor, Anaphylatoxin C5a

Blood Bactericidal Activity

Neuroendocrine Secretory Protein 7B2

Complement Fixation Tests

Receptors, Complement 3d

Serine Endopeptidases

Antigens, CD59

Antigens, CD46

Anaphylatoxins

Molecular Sequence Data

Collectins

Mannose-Binding Lectin

Phagocytosis

Protein Binding

Amino Acid Sequence

Immunoglobulin M

Carboxypeptidase H

Cobra Venoms

Zymosan

Mannose-Binding Protein-Associated Serine Proteases